Compositions and methods for the treatment and analysis of neurological disorders

Abstract

Provided herein are compositions and methods for the treatment and analysis of neurological disorders. In particular, provided herein are small molecules targeted to amyloid-β (Aβ) or metal-Aβ species for the treatment, diagnosis, or study of neurological conditions such as Alzheimer's disease (AD) and other diseases and conditions.

We claim: 
     
         1 - 30 . (canceled) 
     
     
         31 . A compound comprising:
 a) a metal chelation component; and   b) an amyloid β interaction component.   
     
     
         32 . The compound of  claim 31  wherein the compound has a structure according to: 
       
         
           
           
               
               
           
         
         wherein: 
         i) R 1  is selected from the group consisting of H, OH, CH 3 , CO 2 CH 3 , CO 2 H, CH 2 OH, F, O-glucose,  18 F, I,  123 I,  124 I,  125 I,  76 Br, and  77 Br; 
         ii) R 2  is selected from the group consisting of H, OH, NH 2 , NH(CH 3 ), N(CH 3 ) 2 , F, O-glucose,  18 F, I,  123 I,  124 I,  125 I,  76 Br, and  77 Br; and 
         iii) R 3  is each independently selected from the group consisting of H, OH, NH 2 , NH(CH 3 ), N(CH 3 ) 2 , (CH 2 ) n CH 3  (n=1-10), F, O-glucose,  18 F, I,  123 I,  124 I,  125 I,  76 Br, and  77 Br. 
       
     
     
         33 . The compound of  claim 31 , wherein the compound has a structure according to: 
       
         
           
           
               
               
           
         
       
     
     
         34 . The compound of  claim 31  wherein the compound has a structure according to: 
       
         
           
           
               
               
           
         
         wherein each R is independently selected from the group consisting of H, I, F, CH 3 ,  18 F, I,  123 I,  124 I,  125 I,  76 Br, and  77 Br. 
       
     
     
         35 . The compound of  claim 31  wherein the compound penetrates a blood-brain barrier of a human. 
     
     
         36 . A method for treating a subject comprising administering the compound of  claim 31  to a subject. 
     
     
         37 . The method of  claim 36  wherein said subject is a human. 
     
     
         38 . The method of  claim 36 , wherein said subject has a neurological disease or condition. 
     
     
         39 . The method of  claim 38  wherein said neurological disease or condition has amyloid-β (Aβ) plaques as a pathological marker. 
     
     
         40 . The method of  claim 38  wherein said neurological disease or condition is Alzheimer's disease. 
     
     
         41 . The method of  claim 36  wherein said subject has type II diabetes. 
     
     
         42 . The compound of  claim 31  further comprising a label. 
     
     
         43 . The compound of  claim 42  wherein said label is a radionuclide or a substitution bearing a radionuclide. 
     
     
         44 . The compound of  claim 42  wherein said label is a contrast agent. 
     
     
         45 . A method for detecting a compound in a tissue or subject, the method comprising:
 exposing a tissue or subject a compound according to  claim 42 ; and detecting the presence of or accumulation of said compound in said tissue or subject.   
     
     
         46 . The method of  claim 45 , wherein said tissue comprises neural tissue or pancreatic tissue.